Effects of propofol on cyclic AMP response element binding protein phosphorylation and cyclic AMP response element binding protein mRNA expression in hippocampus of rats

Abstract

Objective to investigate the effects of propofol on cyclic AMP response element binding protein (CREB) phosphorylation and CREB mRNA expression in hippocampus of rats. Methods Sixty -four male Sprague -Dawley (SD) rats weighting 250 g-280 g were randomly divided into 2 groups (n=32) with Randomization Adviser 1.0 software: normal saline treated (Group S) and propofol treated (Group P). Animals of both groups underwent a continuous multiple -trial inhibitory avoidance training. The times of trial needed for each animal to attain the learning criterion( 100 seconds) were recorded. Each animal was given intraperitoneal propofol 9 mg/kg or normal saline 2 ml/kg at 15 min before training. The memory retention was tested at 1, 3 and 24 h( n=8, at each time point) after the training session and the memory latency was recorded. Animals were sacrificed at 15 min after reagent administration (T0) and after the memory testing (T1～3). Hippocampus was obtained to determine the phosphorylation of CRKB (pCREB) and CREB mRNA expression. Results The times of trials required for the rats to learn the task in Group S and Group P is 1 (0.25) and 3 (1.25), respectively. Learning ability was significantly impaired in rats of Group P(P<0.01 ). Rats of Group S had a median retention latency more than 300 s at each memory testing. The median retention latency of rats in Group P at T1, T2and T3 was 319( 144) s, 131( 114) s and 56(30) s, respectively. Compared with group S, there was a decrease of CREB phosphorylation expression at T0-3 in Group P (P<0.01). The CREB mRNA expression in Group P was decreased at T3 (P<0.01). Conclusion Propofol can inhibit CREB phosphorylation, and downregulate CREB mRNA expression in hippocampus of rats. Key words: Propofol; DNA-binding protein, cyclic AMP-responsive; Hippocampus